The long-term goal of this research project is to isolate and identify chemical mediators which stimulate the mitosis of undifferentiated stem cells in the olfactory epithelium and lead to their subsequent differentiation and maturation into functioning neurons. The immediate research objectives of this study are four-fold: 1) In order to obtain a workable and controlled experimental system on which to test suspected mediators, embryonic olfactory bulb and olfactory epithelium will be put into co-organ culture. A complete primary olfactory system in culture will allow the continuous observation of morphological and biochemical changes which occur during the degeneration-regeneration process. 2) Embryonic olfactory bulb and olfactory epithelium will be disaggregated and cultured with the purpose of establishing clonal lines of specific cell types. The establishment of clones will facilitate the investigation of the specificity of primary tract innervation, and will also provide a means of identifying the specific location of synthesis, storage, and release of specific biochemical markers and suspected mitotic stimulators. 3) Extracts from olfactory epithelium and bulb will be tested for their ability to affect mitosis, differentiation, and reinnervation in the test organ and cell culture systems. 4) The effects of protein and peptide fractions of tissue extracts and purified peptides, nucleotides, and prostaglandins on tissue culture test systems will be determined.